Numerous compositions useful for administration to persons suffering from neuropathies are known.
In particular, it is known that compositions comprising alpha-lipoic acid have a beneficial effect in the treatment of neuropathies, particularly of acquired peripheral neuropathies. As a matter of fact, alpha-lipoic acid improves the antioxidant barrier and reduces oxidative stress by increasing the levels of glutathione, improves the speed of nerve communication, thus optimizing its functionality, and finally exerts normalizing action against nervous sensitivity, thus reducing both pain and sensory turbidity.
Recent in vivo studies have confirmed the neuroprotective and cardioprotective effects of alpha-lipoic acid.
Quick- or conventional-release compositions comprising dietary alpha-lipoic acid for a single daily administration of 300 mg or 600 mg of alpha-lipoic acid are known.
Published studies “Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy—The SYDNEY 2 trial” Dan Ziegler et. al., Diabetes Care November 2006 vol. 29 no. 11, p. 2365-2370, and “Thioctic Acid and Acetyl-L-Carnitine in the Treatment of Sciatic Pain Caused by a Herniated Disc” Memeo Antonio and Mario Loiero, Clin. Drug Investigation 2008, Vol. 28, p 495-500, report that a daily dose of 600 mg of alpha-lipoic acid provides the best risk/benefit ratio for the treatment of symptoms of diabetic polyneuropathy and sciatic pain. According to the first study, compared to a daily dose of 600 mg, the higher doses of 1200 mg and 1800 mg do not provide a better response in terms of improvement in the symptoms of diabetic polyneuropathy. The study also shows a dose-dependent increase of the side effects related to alpha-lipoic acid, such as nausea, vomiting and dizziness.
It is also known that the bark of Magnolia, a phytoderivative obtained from Magnolia Officinalis, belonging to the family of Magnoliacee, contains two phenolic compounds, honokiol and magnolol. A number of pharmacological properties, such as anti-anxiety, anti-inflammatory, antimicrobial, antioxidant, antiplatelet and neurotrophic properties are ascribed to Magnolia bark.
Y. Fukuyama, Nakade K., Minoshima Y., Yokoyama, A., H. Zhai, Y. Mitsumoto “Neurotrophic activity of honokiol on the cultures of fetal rat cortical neurons,” Bioorg. Med Chem. Lett 2002 Apr. 22; 12 (8):1163-6 describes neurotrophic activities of honokiol at concentrations between 0.1 and 10 μM on cultured rat cortical neurons. In cortical neurons, honokiol is able to promote neurite growth. Furthermore, honokiol has proved capable of increasing the survival and development of neurons of primary cultures.
As regards the neurotrophic activity of honokiol, Lee Y J. et al. “Therapeutic applications of compounds in the magnolia family,” Pharmacol. Ther. 2011, 130 (2): 157-76 describes effective doses in rats ranging from 0.01 g/kg and 0.25 g/kg. There is no known study that shows an effective dosage for humans.
US2006251608 describes formulations for the treatment of aged skin, comprising antioxidants, co-promoters of anti-oxidation, anti-inflammatory agents, vitamins, minerals and promoters of collagen synthesis. It is not mentioned any effectiveness of such formulations for the treatment of neuropathies. Alpha-lipoic acid and honokiol are both mentioned as possible antioxidants in such formulations, but a combination of such compounds is not specifically described.
Nutritional supplements for athletes are known, useful for improving muscle mass, strength and physical strength which include, among many other components, also alpha-lipoic acid and magnolia bark containing 2% honokiol. An effect of these supplements for the treatment of neuropathies is not reported, and the amount of honokiol in such supplements is extremely reduced. In particular, the ratio of honokiol and alpha-lipoic acid in such supplements known turns out to be less than 0.3%.